Electronic nicotine delivery systems (ENDS), popularly known as electronic cigarettes, are promoted as substitutes for cigarettes in places where smoking is not allowed, but also as smoking cessation aids. The World Health Organization Study Group on Tobacco Product Regulation (TobReg) recommended ENDS be subjected to rigorous study to determine if they would have any advantage as a cessation device. Prior to a full clinical trial, however, an assessment of the abuse liability of these devices is required, as is better characterization of the products, and some idea of a recommended dosing schedule. This is a study with three aims: 1) to determine the abuse liability potential of ENDS in a sample of participants motivated to quit smoking. Abuse liability assessment (ALA) will include subjective liking and relief of craving/withdrawal in comparison to own brand commercial cigarette (positive control with known abuse potential), ENDS placebo (sensorimotor effects only), and sham smoking (negative control), self-administration pattern of ENDS while ad lib "smoking," and withdrawal symptoms upon discontinuation of use. ALA will also include comparing neurocognitive function (EEG spectral analysis and evoked brain potentials) during each smoking condition;2) to better characterize ENDS by measuring plasma nicotine boost and ENDS puff topography;3) in order to inform future cessation trials, determine patterns of ad lib use during a cessation attempt. Aims 2 and 3 will also help to provide estimates of effect size and variability for power and sample size estimates for a future cessation trial. Fourteen established cigarette smokers, naive to ENDS, motivated to quit smoking, and 12-hour abstinent, will have four laboratory visits to compare smoking ENDS 16mg, ENDS placebo, own brand commercial cigarettes and sham smoking while EEG is recorded and oddball tasks performed. They will then use ENDS exclusively for two weeks, with four sessions of smoking cessation behavioral counseling. On a final visit, participants will be 12-hours abstinent and return to the laboratory to assess craving/withdrawal from ENDS, smoke ENDS with blood drawn for nicotine boost and recording of "smoking" topography. PUBLIC HEALTH RELEVANCE: It has been suggested that dual weaning from nicotine and some sensorimotor components of the smoking experience could increase quit rates. There is, however, real equipoise about whether ENDS can function as effective and safe smoking cessation aids. Before embarking on an expensive cessation trial utilizing ENDS, abuse liability assessment is warranted, as is a better characterization of ENDS and how best to use them in a smoking cessation trial.